Uptake of organic anions by the liver has kinetic characteristics of facilitated diffusion. Although a carrier or receptor for organic anions has been postulated to be present on the plasma membrane of the hepatocyte, it has not been demonstrated directly. Recent studies of sulphobromophthalein (BSP) have revealed saturable, high affinity binding to rat liver cell plasma membrane with KD equals 4 micrgrams and saturation at 8 micron moles/mg protein. Incubation of membrane with trypsin eliminated binding. Probenecid, an organic anion which competes with bilirubin for liver uptake in vivo, also completed for membrane binding. Rat red cell ghosts did not bind BSP. These results are consistent with existence of an organic anion receptor located on the plasma membrane of the liver cell. Two proteins have been isolated from liver cell plasma membrane (LPM) subfractions by affinity chromatography on BSP-agarose gel. The aim of future studies is to (1) characterize these proteins biochemically with respect to physical characteristics as well as binding properties for organic anions; (2) prepare antibodies to these proteins in goats; (3) localize these proteins within the liver cell by classical cell fractionation techniques as well as histochemical and/or histoimmunologic techniques; (4) determine the functional significance of these proteins in the hepatic transport mechanism by study of organic anion binding and uptake as well as localization of covalent probes in intact liver, isolated hepatocytes, and LPM; (5) identify animal models of abnormal hepatic organic anion uptake in which the possible influence of abnormalities of these proteins can be studied. These models will include regenerating rat liver, mutant Southdown sheep, and liver from thyroidectomized rats.